Recurrent ventricular tachycardia (VT) in the setting of chronic ischemic heart disease is a risk factor for sudden death and a cause of frequent and prolonged hospitalizations in symptomatic patients. To date, the electrophysiologic mechanisms and anatomic basis of this arrhythmia remain poorly understood. The aims of the proposed research are to evaluate, using programmed cardiac stimulation and computer-assisted electrophysiologic mapping techniques in a canine model of chronic transmural myocardial infarction (MI), the electrophysiologic mechanisms of sustained VT, nonsustained (Prefibrillatory) VT, and the transition from VT to ventricular fibrillation (VF). The hypothesis that electrically-inducible sustained VT represents organized reentry in an anatomically small circuit within the ventricles and that electrically inducible non-sustained VT represents an unstable form of disorganized reentry (localized fibrillation) in anatomically small areas of the ventricles will be examined. The significance of changes in QRS-complex morphology and VT rates with regard to the possible presence of multiple reentrant pathways, as opposed to variable sites of exit into the surrounding myocardium from a single pathway, will be assessed using computer-assisted mapping techniques. The relationship between organized and disorganized continuous electrical activity and various properties of sustained and nonsustained VT will be explored in detail. The effects of antiarrhythmic drugs and a variety of pacing interventions on both organized and disorganized continuous electrical activity and sustained and non-sustained VT will also be examined. In addition, long-term ECG recordings will be performed in conjunction with serial electrophysiologic studies in dogs with chronic transmural MI as a possible model for the study of late post-MI sudden death. The relationships between the types and incidence of spontaneous ventricular arrhythmias and the types of electrically inducible ventricular arrhythmias will be analyzed. It is anticipated that these studies will provide new insights into the mechanisms of sustained and nonsustained VT and their relationship to the occurrence of VF in the setting of chronic MI and will contribute to the development of more rational pharmacologic, electrical, and surgical approaches to the prevention of sudden cardiac death.